Device and method for monitoring body fluid and electrolyte disorders

ABSTRACT

Devices and methods for measuring body fluid-related metric using spectrophotometry that may be used to facilitate diagnosis and therapeutic interventions aimed at restoring body fluid balance. In one embodiment, the present invention provides a device for measuring a body-tissue water content metric as a fraction of the fat-free tissue content of a patient using optical spectrophotometry. The device includes a probe housing configured to be placed near a tissue location which is being monitored; light emission optics connected to the housing and configured to direct radiation at the tissue location; light detection optics connected to the housing and configured to receive radiation from the tissue location; and a processing device configured to process radiation from the light emission optics and the light detection optics to compute the metric where the metric includes a ratio of the water content of a portion of patient&#39;s tissue in relation to the lean or fat-free content of a portion of patient&#39;s tissue.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.10/699,610, filed on Oct. 30, 2003, which is a continuation-in-part ofU.S. patent application Ser. No. 10/441,943, filed on May 20, 2003,which is a continuation of U.S. patent application Ser. No. 09/810,918,filed on Mar. 16, 2001, now U.S. Pat. No. 6,591,122, the fulldisclosures of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

The maintenance of body fluid balance is of foremost concern in the careand treatment of critically ill patients, yet physicians have access tofew diagnostic tools to assist them in this vital task. Patients withcongestive heart failure, for example, frequently suffer from chronicsystemic edema, which must be controlled within tight limits to ensureadequate tissue perfusion and prevent dangerous electrolytedisturbances. Dehydration of infants and children suffering fromdiarrhea can be life-threatening if not recognized and treated promptly.

The most common method for judging the severity of edema or dehydrationis based on the interpretation of subjective clinical signs (e.g.,swelling of limbs, dry mucous membranes), with additional informationprovided by measurements of the frequency of urination, heart rate,serum urea nitrogen SUN/creatinine ratios, and blood electrolyte levels.None of these variables alone, however, is a direct and quantitativemeasure of water retention or loss.

The indicator-dilution technique, which provides the most accuratedirect measure of water in body tissues, is the present de factostandard for assessment of body fluid distribution. It is, however, aninvasive technique that requires blood sampling. Additionally, a numberof patents have disclosed designs of electrical impedance monitors formeasurement of total body water. The electrical-impedance technique isbased on measuring changes in the high-frequency (typically 10 KHz-1MHz) electrical impedance of a portion of the body. Mixed results havebeen obtained with the electrical-impedance technique in clinicalstudies of body fluid disturbances as reported by various investigators.The rather poor accuracy of the technique seen in many studies points tounresolved deficiencies of these designs when applied in a clinicalsetting.

Therefore, there exists a need for methods and devices for monitoringbody water fractions which do not suffer from problems due to theirbeing invasive, subjective, inaccurate, and difficult to interpret forthe purpose of clinical diagnosis and intervention.

BRIEF SUMMARY OF THE INVENTION

Embodiments of the present invention provide devices and methods thatmeasure body fluid-related metrics using spectrophotometry that may beused to facilitate diagnosis and therapeutic interventions aimed atrestoring body fluid balance. The disclosed invention facilitates rapid,non-invasive, and continuous measurement of fractional tissue water,f_(w). Additional embodiments facilitate intermittent measurement off_(w). The specifications of source-detector spacings, wavelength rangesof optical measurement, and algorithms for combining the measurements,provide highly accurate and reproducible methods for determination off_(w).

In one embodiment, the present invention provides a device for measuringa body-tissue water content metric as a fraction of the fat-free tissuecontent of a patient using optical spectrophotometry. The deviceincludes a probe housing configured to be placed near a tissue locationwhich is being monitored; light emission optics connected to the housingand configured to direct radiation at the tissue location; lightdetection optics connected to the housing and configured to receiveradiation from the tissue location; and a processing device configuredto process radiation from the light emission optics and the lightdetection optics to compute the metric where the metric includes a ratioof the water content of a portion of patient's tissue in relation to thelean or fat-free content of a portion of patient's tissue.

In another embodiment, the present invention provides a device formeasuring a body-tissue metric using optical spectrophotometry. Thedevice includes a probe housing configured to be placed near a tissuelocation which is being monitored; light emission optics connected tothe housing and configured to direct radiation at the tissue location;light detection optics connected to the housing and configured toreceive radiation from the tissue location; and a processing deviceconfigured to process radiation from the light emission optics and thelight detection optics to compute the metric where the body tissuemetric includes a quantified measure of a ratio of a difference betweenthe water fraction in the blood and the water fraction in theextravascular tissue over the fractional volume concentration ofhemoglobin in the blood.

In another aspect, the present invention provides a method for measuringa body-tissue water content metric in a human tissue location as afraction of the fat-free tissue content of a patient using opticalspectrophotometry. The method includes placing a probe housing near thetissue location; emitting radiation at the tissue location using lightemission optics that are configured to direct radiation at the tissuelocation. The method also includes detecting radiation using lightdetection optics that are configured to receive radiation from thetissue location; and processing the radiation from the light emissionoptics and the light detection optics; and computing the water contentmetric, where the water content metric, f_(w) ^(l) is determined suchthat

${f_{w}^{l} = \frac{\left\lbrack {\sum\limits_{n = 1}^{N}{p_{n}\log\left\{ {R\left( \lambda_{n} \right)} \right\}}} \right\rbrack - {\left\lbrack {\sum\limits_{n = 1}^{N}p_{n}} \right\rbrack\log\left\{ {R\left( \lambda_{N + 1} \right)} \right\}}}{\left\lbrack {\sum\limits_{m = 1}^{M}{q_{m}\log\left\{ {R\left( \lambda_{m} \right)} \right\}}} \right\rbrack - {\left\lbrack {\sum\limits_{m = 1}^{M}q_{m}} \right\rbrack\log\left\{ {R\left( \lambda_{M + 1} \right)} \right\}}}},$and where:p_(n) and q_(m) are calibration coefficients;

-   -   R(λ) is a measure of a received radiation at a wavelength;    -   n=1−N and m=1−M represent indexes for a plurality of wavelengths        which may consist of the same or different combinations of        wavelengths. The method may also include displaying the volume        fraction of water on a display device.

In another embodiment, the present invention provides a method formeasuring a body-tissue metric in a human tissue location using opticalspectrophotometry. The method includes emitting and detecting radiationusing light emission and detection optics. In addition, the methodincludes processing the radiation from light emission and detectionoptics to compute the metric where the body fluid-related metric isrelated to a quantified measure of a ratio of a difference between thewater fraction in the blood and the water fraction in the extravasculartissue over the fractional volume concentration of hemoglobin in theblood. In one aspect, the metric is a water balance index Q, such that:

$Q = {\frac{f_{w}^{IV} - f_{w}^{EV}}{f_{h}^{IV}} = {{a_{1}\frac{\left( {\Delta\;{R/R}} \right)_{\lambda_{1}}}{\left( {\Delta\;{R/R}} \right)_{\lambda_{2}}}} + a_{0}}}$where f_(w) ^(IV) and f_(w) ^(EV) are the fractional volumeconcentrations of water in blood and tissue, respectively, f_(h) ^(IV)is the fractional volume concentration of hemoglobin in the blood,(αR/R)_(λ) is the fractional change in reflectance at wavelength λ, dueto a blood volume change in the tissue, and a₀ and a₁ are calibrationcoefficients.

In another embodiment, the present invention provides a method formeasuring a physiological parameter in a human tissue location. Themethod includes emitting radiation at the tissue location using lightemission optics and detecting radiation using light detection optics.Furthermore, the method includes processing the radiation from the lightemission optics and the light detection optics and computing thephysiological parameter, where the parameter is determined such that itis equal to

$\frac{\left\lbrack {\sum\limits_{n = 1}^{N}{p_{n}\log\left\{ {R\left( \lambda_{n} \right)} \right\}}} \right\rbrack - {\left\lbrack {\sum\limits_{n = 1}^{N}p_{n}} \right\rbrack\log\left\{ {R\left( \lambda_{N + 1} \right)} \right\}}}{\left\lbrack {\sum\limits_{m = 1}^{M}{q_{m}\log\left\{ {R\left( \lambda_{m} \right)} \right\}}} \right\rbrack - {\left\lbrack {\sum\limits_{m = 1}^{M}q_{m}} \right\rbrack\log\left\{ {R\left( \lambda_{M + 1} \right)} \right\}}},$and where:p_(n) and q_(m) are calibration coefficients; R(λ) is a measure of areceived radiation at a wavelength; n=1−N and m=1−M represent indexesfor a plurality of wavelengths which may be the same or differentcombinations of wavelengths. In one aspect, the physiological parameteris a an oxygen saturation values. In another aspect, the physiologicalparameter is a fractional hemoglobin concentration.

In yet another embodiment, the present invention provides a method ofassessing changes in volume and osmolarity of body fluids near a tissuelocation. The method includes emitting radiation at a tissue locationusing light emission optics and detecting radiation using lightdetection optics that are configured to receive radiation from thetissue location. The method also includes processing the radiation fromthe light emission optics and the light detection optics; determining awater balance index using the processed radiation; determining a tissuewater concentration and analyzing in combination the water balance indexand the tissue water concentration to assess changes in volume andosmolarity of body fluids near the tissue location.

For a fuller understanding of the nature and advantages of theembodiments of the present invention, reference should be made to thefollowing detailed description taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing tissue water fraction measured on the ear of apig during an experiment using reflectance measurements at twowavelengths.

FIG. 2 is a graph showing an example regression for prediction of waterfrom reflectances measured at three wavelengths.

FIG. 3 is a graph showing an example regression of a two-wavelengthalgorithm for determination of the difference between the intravascularand extravascular water fraction from pulsatile reflectances measured attwo wavelengths.

FIG. 4 is a diagram of an intermittent-mode version of a fluid monitor.

FIG. 5 is a diagram of a continuous-mode version of a fluid monitor.

FIG. 6 is a block diagram of a handheld apparatus for noninvasivemeasurement and display of tissue water.

FIG. 7 is a bar graph of water content as a percentage of total and leanmass for men and women between the ages of 20 and 79.

FIG. 8 is a bar graph of water content as a percentage of fat-free andfat-free-bone-free mass for men and women between the ages of 20 and 79.

FIG. 9 is a graph of the correlation between separate fat-free or leanvolume water fraction (“f_(w) ^(l)”) measurements on the same patient.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention overcome the problems ofinvasiveness, subjectivity, inaccuracy, and difficulty of interpretationfor the purpose of clinical diagnosis and intervention, from whichprevious methods for body fluid assessment have suffered. The method ofdiffuse reflectance near-infrared (“NIR”) spectroscopy is employed tomeasure the fraction of water in skin. An increase or decrease in thewater content of the skin produces unique alterations of its NIRreflectance spectrum in three primary bands of wavelengths (950-1400 nm,1500-1800 nm, and 2000-2300 nm) in which none-heme proteins (primarilycollagen and elastin), lipids, hemoglobin, and water absorb. Accordingto the results of numerical simulations and experimental studies carriedout by the inventors, the tissue water fraction, f_(w), definedspectroscopically as the ratio of the absorbance of water and the sum ofthe absorbances of water and other constituents of the tissue, can bemeasured accurately in the presence of nonspecific scattering variation,temperature, and other interfering variables.

Various constituents of tissue, other than water, are included in thedenominator of the ratio used to compute the tissue water fractionaccording to the embodiments of the present invention. In oneembodiment, all of the other major tissue constituents, such as non-hemeprotein, lipid (“fat”), and hemoglobin, are included, resulting in thecomputation of the total tissue water fraction, f_(w) ^(T). In otherembodiments, certain constituents of the tissue are specificallyexcluded from the measured tissue water fraction. Spectroscopic methodsfor the removal of certain tissue constituents from the computation oftissue water fraction are disclosed, either by choosing spectral regionswhere the absorbance contribution due to these tissue constituents issmall, or by appropriately combining spectroscopic measurements made atmultiple wavelengths to cancel the absorbance contribution due to thesetissue constituents. The use of such spectroscopic methods for removingthe absorbance contribution due to lipid from the measurement, therebyproviding fractional water in fat-free or lean tissue, f_(w) ^(l), aredescribed. Spectroscopic methods for the exclusion of hemoglobin fromthe fractional water measurement are also disclosed.

In addition to these spectroscopic methods, physical methods forincluding and excluding certain tissue constituents are also describedin the present invention. By disclosing source-detector separations inthe range of 1-5 mm, the present invention targets the dermis,simultaneously avoiding shallow penetration that would be indicativeonly of the outer dead layer of the skin as well as avoiding deeppenetration into the underlying, high fat-content layer, or even furtherinto bone-containing layers. Additional disclosures include theapplication of pressure at the tissue site of the optical measurementallowing various mobile constituents of the tissue to be included orexcluded from the fractional water measurement. In one embodiment, thefractional water is measured before and after the application ofpressure at the tissue site, allowing the mobile intravascular portionof the tissue to be included or excluded from the measurement. By thismeans, measurements of the fractional water content in the intravascularspace, f_(w) ^(IV), extravascular space, f_(w) ^(EV), and a differencebetween the two f_(w) ^(IV)−f_(w) ^(EV), is accomplished. In additionalembodiments, these measurements are accomplished byphotoplethysmography, taking advantage of the natural arterial pulsationof blood through tissue.

In the following detailed descriptions of the embodiments of theinvention, the terms “fractional tissue water”, “tissue water fraction”,“water fraction”, and “f_(w)” all have equivalent meanings and are meantas general terms that include all of the more specific measurementsoutlined above, including, but not limited to, total tissue waterfraction (f_(w) ^(T)), lean tissue water fraction (f_(w) ^(l)),intravascular water fraction (f_(w) ^(IV)), and extravascular waterfraction (f_(w) ^(EV)).

In embodiments of the present invention, the apparatus and itsassociated measurement algorithm are designed according to the followingguidelines:

-   -   1. To avoid the shunting of light through the superficial layers        of the epidermis, the light source and detector in optical        reflectance probe have low numerical apertures, typically less        than 0.3.    -   2. The spacing between the source and detector in the probe is        in the range of 1-5 mm to confine the light primarily to the        dermis.    -   3. The reflectances are measured at wavelengths greater than        approximately 1150 nm to reduce the influence of hemoglobin        absorption. Alternatively, reflectances are measured at        wavelengths as short as 950 nm, but the influence of hemoglobin        absorbance is reduced by appropriately combining measurements of        reflectance at multiple wavelengths. Or as a further        alternative, the absorbance of hemoglobin is intentionally        included in the denominator of the ratio used to compute tissue        water fraction.    -   4. To ensure that the expression that relates the measured        reflectances and water content yields estimates of water        fraction that are insensitive to scattering variations, the        lengths of the optical paths through the dermis at the        wavelengths at which the reflectances are measured are matched        as closely as possible. This matching is achieved by judicious        selection of wavelength sets that have similar water absorption        characteristics. Such wavelength sets may be selected from any        one of the three primary wavelength bands (950-1400 nm,        1500-1800 nm, and 2000-2300 nm) discussed above. Wavelength        pairs or sets are chosen from within one of these three primary        bands, and not from across the bands. More particularly the        wavelength pair of 1180 and 1300 nm is one such wavelength set        where the lengths of the optical paths through the dermis at        these wavelengths are matched as closely as possible.    -   5. To ensure that the expression that relates the measured        reflectances and water fractions yields estimates of water        fraction that are insensitive to temperature variations, the        wavelengths at which the reflectances are measured are chosen to        be either close to temperature isosbestic wavelengths in the        water absorption spectrum or the reflectances are combined in a        way that cancels the temperature dependencies of the individual        reflectances. Typically, absorption peaks of various biological        tissue constituents may shift with variations in temperature.        Here, wavelengths are selected at points in the absorption        spectrum where no significant temperature shift occurs.        Alternately, by knowing the value of this temperature shift,        wavelength sets may be chosen such that any temperature shift is        mathematically canceled out when optical measurements are        combined to compute the value of a tissue water metric. Such        wavelength sets may be selected from any one of the three        primary wavelength bands (950-1400 nm, 1500-1800 nm, and        2000-2300 nm) discussed above. Wavelength pairs or sets are        chosen from within one of these three primary bands, and not        from across the bands. More particularly the wavelength pair of        1180 and 1300 nm are one such pair of temperature isosbestic        wavelengths in the water absorption spectrum.    -   6. The reflectances measured at two or more wavelengths are        combined to form either a single ratio, a sum of ratios, a ratio        of ratios of the form log [R(λ₁)/R(λ₂)], or a ratio of weighted        sums of log [R(λ)] terms, in which the numerator depends        primarily on the absorbance of water and the denominator depends        primarily on the sum of the volume fractions of water and other        specific tissue constituents, such that the denominator is        equally sensitive to a change in the concentration of any of        these specific constituents and water.

Thus, in one embodiment of the present invention the water fraction,f_(w) is estimated according to the following equation, based on themeasurement of reflectances, R(λ) at two wavelengths and the empiricallychosen calibration constants c₀ and c₁:f _(w) =c ₁ log [R(λ₁)/R(λ₂)]+c ₀  (1)

Numerical simulations and in vitro experiments indicate that the totaltissue water fraction, f_(w) ^(T), can be estimated with an accuracy ofapproximately +/−2% over a range of water contents between 50 and 80%using Equation (1), with reflectances R(λ) measured at two wavelengthsand the calibration constants c₀ and c₁ chosen empirically. Examples ofsuitable wavelength pairs are λ₁=1300 nm, λ₂=1168 nm, and λ₁=1230 nm,λ₂=1168 nm.

The ability to measure changes in the total tissue water content in theear of a pig using two-wavelength NIR reflectometry was demonstratedexperimentally in a study in which a massive hemorrhage was induced in apig and the lost blood was replaced with lactated Ringer's solution overa period of several hours. Ringer's solution is a well-known solution ofsalts in boiled and purified water. FIG. 1 shows the total waterfraction in the skin of the ear of a pig, measured using Equation (1)with λ₁=1300 nm and λ₂=1168 nm. Referring to FIG. 1, it should be notedthat experimental observations of concern to this embodiment commencewhen the lactated Ringer's solution was infused 120 minutes after thestart of the experiment. It should also be noted that the drift in thetotal water fraction from approximately 77.5% to 75% before the infusionis not related to this infusion experiment, but is related to thebase-line hemorrhage portion of the experiment. The results show thatthe method of the present embodiment correctly reflects the effect ofthe infusion by showing an increase in total tissue water fraction fromapproximately 75% to 79% while the infusion is continuing. These datasuggest that the disclosed embodiment has a clear value as a monitor ofrehydration therapy in a critical care setting.

In another embodiment of the present invention the water fraction, f_(w)is estimated according to Equation (2) below, based on the measurementof reflectances, R(λ) at three wavelengths and the empirically chosencalibration constants c₀, c₁, and c₂:f _(w) =c ₂ log [R(λ₁)/R(λ₂)]+c ₁ log [R(λ₂)/R(λ₃)]+c ₀  (2)

Better absolute accuracy can be attained using Equation (2) whichincorporates reflectance measurements at an additional wavelength. Theresults of in vitro experiments on excised skin indicate that thewavelength triple (λ₁=1190 nm, λ₂=1170 nm, λ₃=1274 nm) yields accurateestimates of total tissue water content based on Equation (2).

In yet another embodiment of the present invention the water fraction,f_(w) is estimated according to Equation (3) below, based on themeasurement of reflectances, R(λ) at three wavelengths and theempirically chosen calibration constants c₀ and c₁:

$\begin{matrix}{f_{w} = {{c_{1}\frac{\log\left\lbrack {{R\left( \lambda_{1} \right)}/{R\left( \lambda_{2} \right)}} \right\rbrack}{\log\left\lbrack {{R\left( \lambda_{3} \right)}/{R\left( \lambda_{2} \right)}} \right\rbrack}} + c_{0}}} & (3)\end{matrix}$

Better absolute accuracy can be attained using Equations (3), as isattained using Equations (2), which also incorporates reflectancemeasurements at an additional wavelength. Numerical simulations as shownin FIG. 2 indicate that total tissue water accuracy better than +/−0.5%can be achieved using Equation (3), with reflectances measured at threeclosely spaced wavelengths: λ₁=1710 nm, λ₂=1730 nm, and λ₃=1740 nm.Additional numerical simulations indicate that accurate measurement ofthe lean tissue water content, f_(w) ^(l), can be accomplished usingEquation (3), by combining reflectance measurements at 1125, 1185, and1250 nm.

An additional embodiment of the present invention is directed towardsthe measurement of water content as a fraction of fat-free or leantissue content, f_(w) ^(l).

Preferably, a tissue water monitor provides the clinician with anindication of whether the patient requires more, less, or no water toachieve a normo-hydrated state. Such a measurement may be lessuniversally applicable than clinically desired when it is determinedusing an instrument that reports fractional water relative to eithertotal body weight or total tissue content, due to the high variabilityof fat content across the human population. Fat contains very littlewater, so variations in the fractional fat content of the body leaddirectly to variations in the fractional water content of the body. Whenaveraged across many patients, gender and age-related differences in fatcontent, result in systematic variations in water content, a fact thathas been well-documented in the literature, as is shown for example inFIG. 7. Values shown in FIG. 7 are computed from Tables II-III of Cohnet al., J. Lab. Clin. Med. (1985) 105(3), 305-311.

In contrast, when fat is excluded from the calculation, the fractionalwater content, f_(w) ^(l), in healthy subjects, is consistent acrossboth gender and age, as is shown, for example, in FIG. 7. This suggeststhat f_(w) ^(l), can be a more clinically useful measurement than f_(w)for certain conditions. An additional reduction in thesubject-to-subject variation in the “normal” level of fractional watercontent may observed if bone mass is excluded from the calculation, asmay be seen in FIG. 8. This may be due to the fact that the bone contentof the body tends to decrease with age (such as by osteoporosis). Due tothe specified source-detector separations (e.g., 1-5 mm), wavelengthranges, and algorithms, the measurement of f_(w) ^(l) in tissueaccording to the embodiments of the present invention will be closelyrelated to the whole body water content as a fraction of thefat-free-bone-free body content.

In yet another embodiment of the present invention, tissue waterfraction, f_(w), is estimated according to the following equation, basedon the measurement of reflectances, R(λ), at a plurality of wavelengths:

$\begin{matrix}{f_{w} = \frac{\left\lbrack {\sum\limits_{n = 1}^{N}{p_{n}\log\left\{ {R\left( \lambda_{n} \right)} \right\}}} \right\rbrack - {\left\lbrack {\sum\limits_{n = 1}^{N}p_{n}} \right\rbrack\log\left\{ {R\left( \lambda_{N + 1} \right)} \right\}}}{\left\lbrack {\sum\limits_{m = 1}^{M}{q_{m}\log\left\{ {R\left( \lambda_{m} \right)} \right\}}} \right\rbrack - {\left\lbrack {\sum\limits_{m = 1}^{M}q_{m}} \right\rbrack\log\left\{ {R\left( \lambda_{M + 1} \right)} \right\}}}} & (4)\end{matrix}$where p_(n) and q_(m) are calibration coefficients.

An obstacle to the quantification of tissue analytes is the highsubject-to-subject variability of the scattering coefficient of tissue.Determination of the fractional tissue water in accordance with Equation(4) provides similar advantage as that of Equation (3) above, in thatscattering variation is automatically cancelled, especially as long asthe N+1 wavelengths are chosen from within the same wavelength band(950-1400 nm, 1500-1800 nm, or 2000-2300 nm). An explanation of themanner in which Equation (4) automatically cancels scattering variationsis provided below.

Tissue reflectance can be modeled according to a modified form of theBeer-Lambert equation:

$\begin{matrix}{{\log\left\{ {R(\lambda)} \right\}} = {{{- {l(\lambda)}}{\sum\limits_{j = 1}^{J}{c_{j}{ɛ_{j}(\lambda)}}}} - {\log\left\{ {I_{0}(\lambda)} \right\}}}} & (5)\end{matrix}$

where R is the tissue reflectance, l is the mean pathlength of light atwavelength λ, ε_(j) and c_(j) are the extinction coefficient andconcentration of constituent j in the tissue, and log {I₀(λ)} is ascattering offset term. According to this model, the scatteringdependence of tissue reflectance is due to the offset term, log {I₀(λ)},and the pathlength variation term, l(λ). Since the scatteringcoefficient varies slowly with wavelength, by selecting all of thewavelengths from within the same wavelength band, the wavelengthdependence of the scattering coefficient can be ignored to a goodapproximation. Under these conditions, by multiplying the log of thereflectance at wavelength N+1 (or M+1) by the negative of the sum of thecoefficients used to multiply the log of the reflectances at the N (orM) other wavelengths, the scattering offset terms are cancelled in boththe numerator and denominator of Equation (4). This can be seen, forexample, by substituting Equation (5) into the numerator of Equation(4):

$\begin{matrix}{{\left\lbrack {\sum\limits_{n = 1}^{N}{p_{n}\log\left\{ {R\left( \lambda_{n} \right)} \right\}}} \right\rbrack - {\left\lbrack {\sum\limits_{n = 1}^{N}p_{n}} \right\rbrack\log\left\{ {R\left( \lambda_{N + 1} \right)} \right\}}} = {{{- l}{\sum\limits_{n = 1}^{N}\left\lbrack {p_{n}{\sum\limits_{j = 1}^{J}{c_{j}{ɛ_{j}\left( \lambda_{n} \right)}}}} \right\rbrack}} + {{l\left\lbrack {\sum\limits_{n = 1}^{N}p_{n}} \right\rbrack}{\sum\limits_{j = 1}^{J}{c_{j}{ɛ_{j}\left( \lambda_{N + 1} \right)}}}}}} & (6)\end{matrix}$

A review of Equation (6) shows that the scattering offset term has beencancelled, but the scattering dependent pathlength variation term, l,remains. When the numerator and denominator of Equation (4) arecombined, the pathlength variation term is also cancelled, as shown inEquation (7):

$\begin{matrix}{f_{w} = \frac{{- {\sum\limits_{n = 1}^{N}\left\lbrack {p_{n}{\sum\limits_{j = 1}^{J}{c_{j}{ɛ_{j}\left( \lambda_{n} \right)}}}} \right\rbrack}} + {\left\lbrack {\sum\limits_{n = 1}^{N}p_{n}} \right\rbrack{\sum\limits_{j = 1}^{J}{c_{j}{ɛ_{j}\left( \lambda_{N + 1} \right)}}}}}{{- {\sum\limits_{m = 1}^{M}\left\lbrack {q_{m}{\sum\limits_{j = 1}^{J}{c_{j}{ɛ_{j}\left( \lambda_{m} \right)}}}} \right\rbrack}} + {\left\lbrack {\sum\limits_{m = 1}^{M}q_{m}} \right\rbrack{\sum\limits_{j = 1}^{J}{c_{j}{ɛ_{j}\left( \lambda_{M + 1} \right)}}}}}} & (7)\end{matrix}$

A review of Equation (7) shows that Equation (7) depends only on theconcentrations and extinction coefficients of the constituents of tissueand on the calibration coefficients p_(n) and q_(m).

In addition to providing for variable scattering compensation, themethods using Equation (4) allow a more general implementation byrelaxing some of the constraints that are imposed by the use of Equation(3), above. For example:

(a) In order to provide a certain level of accuracy for measurement off_(w), the numerator in Equation (3) may need to be sensitive to changesin water concentration but insensitive to changes in all other tissueconstituents. For example, Equation (3) may require that the absorbanceof all tissue constituents besides water (e.g. lipid, non-heme protein,hemoglobin) are nearly equal at wavelengths 1 and 2. This constraint isremoved in Equation (4), where the coefficients p_(n) are chosen tocancel out absorbance by all tissue constituents other than water.

(b) In order to provide a certain level accuracy for measurement off_(w), the denominator in Equation (3) may need to be equally sensitiveto concentration changes of all tissue constituents to which the waterfraction is to be normalized. In addition, Equation (3) may require thatthe absorbance be equal at wavelengths 2 and 3 for all tissueconstituents to be excluded from the water fraction normalization. Thisconstraint is removed in Equation (4), where the coefficients, q_(m),can be chosen to cancel the absorbance contribution due to certainconstituents, while equalizing the absorbance sensitivity to theremaining tissue constituents.

In the case of measurement of the water fraction in lean tissue, f_(w)^(l), the coefficients, p_(n), in the numerator of Equation (4) arechosen to cancel the contribution from all of the major light-absorbingconstituents of tissue, except water. Similarly, the coefficients,q_(m), in the denominator of Equation (4) are chosen to cancel thecontribution from all tissue constituents other than water and protein.In addition, the coefficients, q_(m), are chosen to equalize thesensitivity of the denominator to changes in water and protein on avolume fractional basis. By computing the ratio of these two terms, theresult is a fractional volume measurement of water concentration in leantissue.

In addition, application of Equation (4) to the measurement offractional water content in total tissue volume, f_(w) ^(T), isaccomplished by choosing the coefficients in the denominator of Equation(4), q_(m), so that all tissue constituents (including lipid) areequalized on a fractional volume basis.

By relaxing some of the constraints imposed by Equation (3), the use ofEquation (4) can be expected to produce a more accurate prediction offractional tissue water content, for the reasons set forth above.Various wavelength combinations may be used based on the criteriadisclosed above. In order to select one wavelength combination for usewith Equation (4) for the purpose of measuring fractional water contentin lean tissue, f_(w) ^(l), extinction coefficients of the majorabsorbing constituents of tissue (water, non-heme protein, lipid, andhemoglobin) were experimentally measured and various wavelengthcombinations of these were applied to a numerical model of tissueabsorbance. The reproducibility of the algorithms incorporating the mostpromising of these wavelength combinations were then compared using realtissue data. The real tissue data were collected from 37 differentvolunteers at a local hospital, with Institutional Review Board (IRB)approval. The sensor measured reflected light from the pad of thefinger, with a source-detector spacing of approximately 2.5 mm. Thesensor was completely removed from the tissue between each pair ofmeasurements. One such preferred algorithm combines measurements at 4wavelengths, namely: 1180, 1245, 1275, and 1330 nm. Using this selectionof wavelengths, the measurement-to-measurement reproducibility, as shownin FIG. 9, is 0.37%, indicating high reproducibility of the tissue watermeasurements using the methods disclosed herein.

In addition to providing a method for measuring tissue water fraction,the method in accordance with Equation (4) above, also has generalutility for the fractional quantification of analytes in tissue. Ingeneral, by appropriate choice of wavelengths and coefficients, Equation(4) is extendible to the fractional concentration measurement of anytissue constituent or combination of constituents in tissue with respectto any other constituent or combination of constituents. For example,this equation is also applicable for the determination of the fractionalhemoglobin content in tissue.

Thus, in one embodiment of the present invention, the fractional volumeof total hemoglobin in tissue is determined using Equation (4) bycombining reflectance measurements at wavelengths where hemoglobin isstrongly absorbing with reflectance measurements where the remainingtissue constituents (such as water, lipid, and non-protein) are stronglyabsorbing. The coefficients, p_(n), in the numerator of Equation (4) arechosen to cancel the absorbance contributions from all tissueconstituents except total hemoglobin. The coeffients, q_(m), in thedenominator of Equation (4) are chose to equalize the absorbancecontributions of all major tissue constituents, on a volume fractionalbasis. One specific wavelength combination for accomplishing thismeasurement is 805 nm, 1185 nm, and 1310 nm. At 805 nm the absorbance bythe oxy- and deoxyhemoglobin are approximately equal. At 1185 nm, theabsorbance of water, non-heme protein, and lipid, are nearly equal on afractional volume basis. At 1300 nm the tissue absorbance will bedominated by water.

In another embodiment of the present invention, measurement offractional concentrations of different species of hemoglobin in tissueis performed. In general, the method provides a means of measuring thefractional concentration of hemoglobin in a first set comprised of oneor more species of hemoglobin with respect to the concentration ofhemoglobin in a second set comprised of one or more hemoglobin speciesin tissue. The coefficients, p_(n), in the numerator of Equation (4) arechosen to cancel the absorbance contributions from all tissueconstituents except the hemoglobin species included in set 1. Thecoeffients, q_(m), in the denominator of Equation (4) are chose toequalize the absorbance contributions from all tissue constituentsexcept the hemoglobin species included in set 2. Sets 1 and 2 aresubsets of hemoglobin species that are present in the body tissue orblood. For example, such hemoglobin species include oxyhemoglobin,deoxyhemoglobin, carboxyhemoglobin, methemoglobin, sulftlemoglobin and,so on. And in general, as used herein, other physiological parametershave other subsets of constituents each being capable of absorbing atdifferent wavelengths. In the case where set 1 is comprised ofoxy-hemoglobin and set 2 is comprised of oxy- and deoxyhemoglobin, aspecific wavelength combination for accomplishing the measurement is735, 760, and 805 nm.

Individuals skilled in the art of near-infrared spectroscopy wouldrecognize that, provided that the aforementioned guidelines arefollowed, additional terms can be added to Equations (1)-(4) and whichmay be used to incorporate reflectance measurements made at additionalwavelengths and thus improve accuracy further.

An additional embodiment of the disclosed invention provides the abilityto quantify shifts of fluid into and out of the bloodstream through anovel application of pulse spectrophotometry. This additional embodimenttakes advantage of the observation that pulsations caused by expansionof blood vessels in the skin as the heart beats produce changes in thereflectance at a particular wavelength that are proportional to thedifference between the effective absorption of light in the blood andthe surrounding interstitial tissues. Numerical simulation indicatethat, if wavelengths are chosen at which water absorption issufficiently strong, the difference between the fractions of water inthe blood, f_(w) ^(IV) and surrounding tissue, f_(w) ^(EV) isproportional to the ratio of the dc-normalized reflectance changes(ΔR/R) measured at two wavelengths, according to Equation (8) below:

$\begin{matrix}{{{f_{w}^{EV} - f_{w}^{IV}} = {{c_{1}\frac{\left( {\Delta\;{R/R}} \right)_{\lambda_{1}}}{\left( {\Delta\;{R/R}} \right)_{\lambda_{2}}}} + c_{0}}},} & (8)\end{matrix}$where c₀ and c₁ are empirically determined calibration constants. Thisdifference, integrated over time, provides a measure of the quantity offluid that shifts into and out of the capillaries. FIG. 3 shows theprediction accuracy expected for the wavelength pair λ₁=1320 nm andλ₂=1160 nm.

An additional embodiment of the present invention is directed towardsthe measurement of water balance index, Q, such that:

$\begin{matrix}{Q = {\frac{f_{w}^{IV} - f_{w}^{EV}}{f_{h}^{IV}} = {{a_{1}\frac{\left( {\Delta\;{R/R}} \right)_{\lambda_{1}}}{\left( {\Delta\;{R/R}} \right)_{\lambda_{2}}}} + a_{0}}}} & (9)\end{matrix}$

where f_(h) ^(IV) is the fractional volume concentration of hemoglobinin the blood, and a₀ and a₁ are calibration coefficients. The use ofEquation (9) to determine a water balance is equivalent to usingEquation (8) above, where f_(h) ^(IV) is set equal to 1. However, usingEquation (9) provides for a more accurate determination by notneglecting the influence of f_(h) ^(IV) on the derived result. Theeffect of this omission can be understood by allowing total hemoglobinto vary over the normal physiological range and computing the differencebetween the results provided by Equation (9) when f_(h) ^(IV) is fixedor allowed to vary. For example, when calculations were performed withf_(w) ^(EV) fixed at 0.65, f_(w) ^(IV) varying between 0.75 and 0.80,and f_(h) ^(IV) varying between 0.09 and 0.135 or held fixed at 0.112,the resulting error was as large as +/−20%. In situations of extremeblood loss or vascular fluid overload (hypo- or hypervolemia) the errorcould be larger.

The quantity Q, provided by Equation (9) may be combined with a separatemeasurement of fractional hemoglobin concentration in blood, f_(h)^(IV), (such as may be provided by standard clinical measurements ofhematocrit or total hemoglobin) in order to provide a measure of thedifference between the intravascular and extravascular water content,f_(w) ^(IV)−f_(w) ^(EV). Alternatively, the quantity Q, may haveclinical utility without further manipulation. For example, by providinga simultaneous measurement of both Q and fractional tissue water (eitherf_(w) or f_(w) ^(l)), the embodiments of the present invention enablethe provision of a clinical indication of changes in both volume andosmolarity of body fluids. Table 1 lists the 6 combinations of volumeand osmolarity changes in body fluids that are clinically observed (fromPhysiology, 2^(nd) Edition, Linda S. Costanzo, Williams and Wilkins,Baltimore, 1998, pg. 156), and the expected direction and magnitude ofthe resultant change in fractional volume of water in blood (F_(w)^(IV)), the fractional volume of water in tissue (f_(w) ^(EV)), thefractional volume of hemoglobin in blood (f_(h) ^(IV)), the numerator ofQ (Q_(n)), the inverse of the denominator of Q (1/Q_(d)), the combinedresult (Q_(n)/Q_(d)=Q), and the fractional volume of water in leantissue, f_(w) ^(l). Taking the first row of Table 1 as an example, theresult of isosmotic volume expansion, such as may be brought about byinfusion with isotonic saline, would result in an increase in thefraction of water in blood (f_(w) ^(IV)), a small increase in theextravascular water fraction (f_(w) ^(EV)), and a large decrease in thefractional concentration of hemoglobin in the blood (f_(h) ^(IV)). Thecombined effect of these 3 factors would result in a large increase inQ. A small increase in the fraction of water in the lean tissue, f_(w)^(l), would also be expected. Notice that when Q and f_(w) ^(l) areviewed in combination, they provide unique signatures for each of the 6types of fluid balance change listed in Table 1. An instrument providingthese measurements in a non-invasive and continuous fashion is thus ableto provide a powerful tool for the monitoring of tissue water balance.

Table 1. Expected changes in Q and f_(w) ^(l) resulting from changes inbody fluid volume and osmolarity

Type Example f_(w) ^(IV) f_(w) ^(EV) f_(h) ^(IV) Q_(n) 1/Q_(d) Q f_(w) ¹Isosmotic volume expansion Isotonic NaCl Infusion

Isosmotic volume contraction Diarrhea

Hyperosmotic volume expansion High NaCl intake

0 Hyperosmotic volume contraction Sweating, Fever

0

Hyposmotic volume contraction SIADH

0

Hyposmotic volume contraction Adrenal Insufficiency

0

FIGS. 4 and 5 show diagrams of two different versions of an instrumentfor measuring the amount of water in body tissues. The simplest versionof the instrument 400 shown in FIG. 4 is designed for handheld operationand functions as a spot checker. Pressing the spring-loaded probe head410 against the skin 412 automatically activates the display of percenttissue water 414. The use of the spring-loaded probe head provides theadvantages of automatically activating the display device when neededand turning the device off when not in use, thereby extending device andbattery life. Moreover, this unique use of a spring-loaded probe alsoprovides the variable force needed to improve the reliability ofmeasurements. Percent tissue water represents the absolute percentage ofwater in the skin beneath the probe (typically in the range 0.6-0.9). Inone embodiment of the present invention, the force exerted by a springor hydraulic mechanism (not shown) inside the probe head 410 isminimized, so that the fluid content of the tissue beneath the probe isnot perturbed by its presence. In this manner, the tissue waterfraction, including both intravascular and extravascular fluid fractionsis measured. In another embodiment of the invention, the force exertedby the probe head is sufficient to push out most of the blood in theskin below the probe to allow measurement of only the extravascularfluid fraction. A pressure transducer (not shown) within the probe head410 measures the compressibility of the skin for deriving an index ofthe fraction of free (mobile) water.

The more advanced version of the fluid monitor 500 shown in FIG. 5 isdesigned for use as a critical-care monitor. In addition to providing acontinuous display of the volume fraction of water 510 at the site ofmeasurement 512, it also provides a trend display of the time-averageddifference between the intravascular fluid volume (“IFV”) andextravascular fluid volume (“EFV”) fractions (e.g., IFV−EFV=f_(w)^(IV)−f_(w) ^(EV)) 514 or the quantity Q (as defined above withreference to Equation (9), updated every few seconds. This latterfeature would give the physician immediate feedback on the net movementof water into or out of the blood and permit rapid evaluation of theeffectiveness of diuretic or rehydration therapy. To measure the IFV−EFVdifference or Q, the monitor records blood pulses in a manner similar toa pulse oximeter. Therefore, placement of the probe on the finger orother well-perfused area of the body would be required. In cases inwhich perfusion is too poor to obtain reliable pulse signals, theIFV−EFV or Q display would be blanked, but the tissue water fraction(f_(w)) would continue to be displayed. A mechanism for mechanicallyinducing the pulse is built into the probe to improve the reliability ofthe measurement of IFV−EFV or Q under weak-pulse conditions.

FIG. 6. is a block diagram of a handheld device 600 for measuring tissuewater fraction, as well as shifts in water between the IFV and EFVcompartments, or a measurement of Q, with a pulse inducing mechanism.Using this device 600, patient places his/her finger 610 in the probehousing. Rotary solenoid 612 acting through linkage 614 and collar 616induces a mechanical pulse to improve the reliability of the measurementof IFV−EFV or Q. LEDs 618 emit light at selected wavelengths andphotodiode 620 measure the transmitted light. Alternately, thephotodiode 620 can be placed adjacent to the LEDs to allow for themeasurement of the reflectance of the emitted light. Preamplifier 622magnifies the detected signal for processing by the microprocessor 624.Microprocessor 624, using algorithms described above, determines thetissue water fraction (f_(w)) (such as in the total tissue volume (f_(w)^(T)), within the lean tissue volume (f_(w) ^(l)), and/or within the IFV(f_(w) ^(IV)) and the EFV (f_(w) ^(EV))), as well as shifts in waterbetween the IFV and EFV (such as IFV−EFV or Q), and prepares thisinformation for display on display device 626. Microprocessor 624 isalso programmed to handle the appropriate timing between the rotarysolenoid's operation and the signal acquisition and processing. In oneembodiment, a means is provided for the user to input the fractionalhemoglobin concentration (f_(h) ^(IV)) or a quantity proportional tof_(h) ^(IV) (such as hematocrit or total hemoglobin) in order to convertQ into IFV−EFV. The design of the device and the microprocessorintegrates the method and apparatus for reducing the effect of noise onmeasuring physiological parameters as described in U.S. Pat. No.5,853,364, assigned to Nellcor Puritan Bennett, Inc., the entiredisclosure of which is hereby incorporated herein by reference.Additionally, the design of the device and the microprocessor alsointegrates the electronic processor as described in U.S. Pat. No.5,348,004, assigned to Nellcor Incorporated, the entire disclosure ofwhich is hereby incorporated herein by reference.

As will be understood by those skilled in the art, other equivalent oralternative methods for the measurement of the water fraction withintissue (f_(w)), as well as shifts in water between the intravascular andextravascular compartments, IVF−EVF or Q, according to the embodimentsof the present invention can be envisioned without departing from theessential characteristics thereof. For example, the device can beoperated in either a handheld or a tabletop mode, and it can be operatedintermittently or continuously. Moreover, individuals skilled in the artof near-infrared spectroscopy would recognize that additional terms canbe added to the algorithms used herein to incorporate reflectancemeasurements made at additional wavelengths and thus improve accuracyfurther. Also, light sources or light emission optics other then LED'sincluding and not limited to incandescent light and narrowband lightsources appropriately tuned to the desired wavelengths and associatedlight detection optics may be placed within the probe housing which isplaced near the tissue location or may be positioned within a remoteunit; and which deliver light to and receive light from the probelocation via optical fibers. Additionally, although the specificationdescribes embodiments functioning in a back-scattering or a reflectionmode to make optical measurements of reflectances, other embodiments canbe working in a forward-scattering or a transmission mode to make thesemeasurements. These equivalents and alternatives along with obviouschanges and modifications are intended to be included within the scopeof the present invention. Accordingly, the foregoing disclosure isintended to be illustrative, but not limiting, of the scope of theinvention which is set forth in the following claims.

What is claimed is:
 1. A method of assessing changes in volume andosmolarity of body fluids in a body tissue, comprising: using a sensor:emitting radiation at a tissue location using light emission opticsconfigured to direct radiation of a given wavelength at the tissuelocation; detecting radiation using light detection optics configured toreceive radiation from the tissue location; converting the detectedradiation to an electrical signal indicative of the radiation receivedby the light detection optics; using a processor: processing theelectrical signal to determine a water balance index and a tissue waterconcentration, wherein the water balance index comprises a differencebetween a water fraction in blood and a water fraction in extravasculartissue; and analyzing in combination the water balance index and thetissue water concentration to assess the changes in volume andosmolarity of body fluids near the tissue location.
 2. The method ofclaim 1 wherein the water balance index comprises a ratio of adifference between the water fraction in the blood and the waterfraction in the extravascular tissue over a fractional volumeconcentration of hemoglobin in the blood.
 3. The method of claim 1wherein the tissue water concentration comprises a volume fractionalwater concentration.
 4. The method of claim 1 wherein analyzing incombination the water balance index and the tissue water concentrationto assess the changes in volume and osmolarity of body fluids near thetissue location comprises integrating over time the difference between awater fraction in the blood and a water fraction in the extravasculartissue.
 5. The method of claim 1 wherein determining the water balanceindex, Q, comprises:$Q = {\frac{f_{w}^{IV} - f_{w}^{EV}}{f_{h}^{IV}} = {{a_{1}\;\frac{\left( {\Delta\;{R/R}} \right)_{\lambda_{1}}}{\left( {\Delta\;{R/R}} \right)_{\lambda_{2}}}} + a_{0}}}$where f_(w) ^(IV) and f_(w) ^(EV) are fractional volume concentrationsof water in blood and tissue, respectively, f_(h) ^(IV) is a fractionalvolume concentration of hemoglobin in the blood, (ΔR/R)_(λ) is afractional change in reflectance at wavelength λ due to a blood volumechange in the tissue, and a₀ and a₁ are calibration coefficients.
 6. Themethod of claim 1 comprising combining the water balance index with aseparate clinical measurement of fractional volume concentration ofhemoglobin in the blood to provide for a measure of the differencebetween intravascular and extravascular water content.
 7. A method ofprocessing changes in volume and osmolarity of body fluids in a bodytissue, comprising: using a processor: processing electrical signalsindicative of radiation received from the body tissue to determine awater balance index and determine a tissue water concentration, whereinthe water balance index comprises a difference between a water fractionin blood and a water fraction in extravascular tissue; and analyzing thewater balance index and the tissue water concentration to assess thechanges in volume and osmolarity of body fluids in the body tissue. 8.The method of claim 7 wherein the water balance index comprises a ratioof a difference between the water fraction in the blood and the waterfraction in the extravascular tissue over a fractional volumeconcentration of hemoglobin in the blood.
 9. The method of claim 7wherein the tissue water concentration comprises a volume fractionalwater concentration.
 10. The method of claim 7 wherein analyzing thewater balance index and the tissue water concentration to assess thechanges in volume and osmolarity of body fluids in the body tissuecomprises integrating over time the difference between the waterfraction in the blood and the water fraction in the extravasculartissue.
 11. The method of claim 7 wherein determining the water balanceindex, Q, comprises:$Q = {\frac{f_{w}^{IV} - f_{w}^{EV}}{f_{h}^{IV}} = {{a_{1}\;\frac{\left( {\Delta\;{R/R}} \right)_{\lambda_{1}}}{\left( {\Delta\;{R/R}} \right)_{\lambda_{2}}}} + a_{0}}}$where f_(w) ^(IV) and f_(w) ^(EV) are fractional volume concentrationsof water in blood and tissue, respectively, f_(h) ^(IV) is a fractionalvolume concentration of hemoglobin in the blood, (ΔR/R)_(λ) is afractional change in reflectance at wavelength λ due to a blood volumechange in the tissue, and a₀ and a₁ are calibration coefficients. 12.The method of claim 7 comprising combining the water balance index witha separate clinical measurement of fractional volume concentration ofhemoglobin in the blood to provide for a measure of the differencebetween intravascular and extravascular water content.
 13. A device forassessing changes in volume and osmolarity of body fluids in a bodytissue, comprising: means for emitting radiation at a tissue locationusing light emission optics configured to direct radiation of a givenwavelength at the tissue location; means for detecting radiation usinglight detection optics configured to receive radiation from the tissuelocation; means for converting the detected radiation to an electricalsignal indicative of the radiation received by the light detectionoptics; means for processing the electrical signal to determine a waterbalance index and a tissue water concentration, wherein the waterbalance index comprises a difference between a water fraction in bloodand a water fraction in extravascular tissue; and means for analyzing incombination the water balance index and the tissue water concentrationto assess the changes in volume and osmolarity of body fluids near thetissue location.
 14. The device of claim 13 wherein the water balanceindex comprises a ratio of a difference between the water fraction inthe blood and the water fraction in the extravascular tissue over afractional volume concentration of hemoglobin in the blood.
 15. Thedevice of claim 13 wherein the tissue water concentration comprises avolume fractional water concentration.
 16. The device of claim 13wherein the means for analyzing in combination the water balance indexand the tissue water concentration to assess the changes in volume andosmolarity of body fluids near the tissue location comprises means forintegrating over time the difference between a water fraction in theblood and a water fraction in the extravascular tissue.
 17. The deviceof claim 13 wherein determining the water balance index, Q, comprises:$Q = {\frac{f_{w}^{IV} - f_{w}^{EV}}{f_{h}^{IV}} = {{a_{1}\;\frac{\left( {\Delta\;{R/R}} \right)_{\lambda_{1}}}{\left( {\Delta\;{R/R}} \right)_{\lambda_{2}}}} + a_{0}}}$where f_(w) ^(IV) and f_(w) ^(EV) are fractional volume concentrationsof water in blood and tissue, respectively, f_(h) ^(IV) is a fractionalvolume concentration of hemoglobin in the blood, (ΔR/R)_(λ) is afractional change in reflectance at wavelength λ due to a blood volumechange in the tissue, and a₀ and a₁ are calibration coefficients. 18.The device of claim 13 comprising means for combining the water balanceindex with a separate clinical measurement of fractional volumeconcentration of hemoglobin in the blood to provide for a measure of thedifference between intravascular and extravascular water content.
 19. Adevice for processing changes in volume and osmolarity of body fluids ina body tissue, comprising: means for processing electrical signalsindicative of radiation received from the body tissue to determine awater balance index and determine a tissue water concentration, whereinthe water balance index comprises a difference between a water fractionin blood and a water fraction in extravascular tissue; and means foranalyzing the water balance index and the tissue water concentration toassess the changes in volume and osmolarity of body fluids in the bodytissue.
 20. The device of claim 19 wherein the water balance indexcomprises a ratio of a difference between the water fraction in theblood and the water fraction in extravascular tissue over a fractionalvolume concentration of hemoglobin in the blood.
 21. The device of claim19 wherein the tissue water concentration comprises a volume fractionalwater concentration.
 22. The device of claim 19 wherein the means foranalyzing the water balance index and the tissue water concentration toassess the changes in volume and osmolarity of body fluids in the bodytissue comprises means for integrating over time the difference betweenthe water fraction in the blood and the water fraction in theextravascular tissue.
 23. The device of claim 7 wherein determining thewater balance index, Q, comprises:$Q = {\frac{f_{w}^{IV} - f_{w}^{EV}}{f_{h}^{IV}} = {{a_{1}\;\frac{\left( {\Delta\;{R/R}} \right)_{\lambda_{1}}}{\left( {\Delta\;{R/R}} \right)_{\lambda_{2}}}} + a_{0}}}$where f_(w) ^(IV) and f_(w) ^(EV) are fractional volume concentrationsof water in blood and tissue, respectively, f_(h) ^(IV) is a fractionalvolume concentration of hemoglobin in the blood, (ΔR/R)_(λ) is afractional change in reflectance at wavelength λ due to a blood volumechange in the tissue, and a₀ and a₁ are calibration coefficients. 24.The device of claim 19 comprising means for combining the water balanceindex with a separate clinical measurement of fractional volumeconcentration of hemoglobin in the blood to provide for a measure of thedifference between intravascular and extravascular water content.